Amine catalysts, secondary amides

Other Rea.ctlons, The anhydride of neopentanoic acid, neopentanoyl anhydride [1538-75-6] can be made by the reaction of neopentanoic acid with acetic anhydride (25). The reaction of neopentanoic acid with acetone using various catalysts, such as titanium dioxide (26) or 2irconium oxide (27), gives 3,3-dimethyl-2-butanone [75-97-8] commonly referred to as pinacolone. Other routes to pinacolone include the reaction of pivaloyl chloride [3282-30-2] with Grignard reagents (28) and the condensation of neopentanoic acid with acetic acid using a rare-earth oxide catalyst (29). Amides of neopentanoic acid can be prepared direcdy from the acid, from the acid chloride, or from esters, using primary or secondary amines. 

Catalytic hydrogenation of amides to amines requires drastic conditions in general, a temperature of 250 to 265" and a pressure of 200 to 300 atm. over copper-chromium oxide catalyst using dioxane as the solvent. The yields of primary amines from unsubstituted amides are lowered mainly by the formation of secondary amines, viz.,... 

Interestingly, the presence of a bis-homopropargylic secondary amide does not lead to insertion into the N-H (as happens with a tungsten catalyst [8c]) competing with formation of the dihydropyran as shown in Equation 1.4 [10]. This reaction extends to the insertion into a phenolic OH to form benzofurans (Equation 1.5). In this case, the presence of an amine such as n-butylamine or pyridine appears to be required [11]. It should be noted that insertion into the benzylic OH to form the pyran system does not compete. 

The heptanuclear iron carbonyl cluster [Fe3(CO)u(/u-H)]2-Fe(DMF)4 (178) acted as an efficient catalyst in the reduction of carboxamides by l,2-bis(dimethylsilyl)benzene in toluene to the corresponding amines in high yields. Several tertiary and secondary amides including a sterically crowded amide were also reduced smoothly A review of the development of optically active cobalt complex catalysts for enan-tioselective synthetic reactions has addressed the applications of ketoiminatocobalt(II) complexes such as (5)-MPAC (179) and (5)-AMAC (180), transition-state models for borohydride reduction, halogen-free reduction by cobalt-carbene complexes. 

Potassium fluoride in combination with alumina has been shown to be a good catalyst for the iV-alkylation of carboxamides, lactams and other N-heterocycles using alkyl halides or dialkyl sulfates under mild conditions [47]. The system was also used to AT-alkylate secondary amides and N,N-dialkylate primary amides. Potassium hydroxide and alumina make a useful combination for the catalysis of the selective mono-AT-alkylation of primary amines (e.g. equation 4.6) [48]. 

Lanthanide amides Ln[N(SiMe3)2]3()tt-Cl)Li(THF)3 or Ln[N(SiMe3)2]3 have been reported to be efficient catalysts for amidation of aldehydes with amines under mild conditions without the use of peroxide and base. But this kind of catalyst is not suitable for the amidation of aldehydes with secondary cycUc amines. Heterobimetallic lanthanide/alkali metal complexes stabilized by phenolate ligand are new classes of bimetallic catalysts for amidation of... 

Silver(I) salts are often utilized as catalysts for addition reactions. Kozmin and Sun have recently shown that AgNTf2 is a catalyst of choice for the hydroamination of siloxy alkynes with either secondary amides or carbamates to give silyl ketene am-inals [34]. The addition occurs in a syn selective manner, for instance, the reaction of siloxy alkyne (24) with carbamate (25) produces silyl ketene aminal (26) in 86% yield at room temperature under the influence of 1 mol% of AgNTf2 (Scheme 18.9). A six-membered chelated transition state is proposed to explain the high syn selectivity. Diastereoselective bromohydroxylation and bromomethoxylation reactions of cinnamoyl compounds possessing a chiral auxiliary are also effectively promoted by silver(I) salts such as AgNOs [35]. The asymmetric halohydrin reaction has been successfully applied into stereoselective syntheses of (-)-chloramphenicol and (+)-thiamphenicol. Csp-H iodination [36], hydrosilylation of aldehydes [37], and deprotection of TMS-alkynes [38] are also catalyzed by silver (I) salts. 

Buchwald and co-workers reported that the combination of air stable Cul (instead of the air sensitive CuOTf) and racemic trans-1,2-cyclohexanediamine (ligand la), in the presence of K3PO4, K2CO3, CS2CO3, or f-BuONa comprises an extremely efficient and general catalyst for the iV-amidation of aryl and heteroaryl halides (eq 9) and the Ai-arylation of a number of heterocycles (eq 10). This approach tolerates functional groups such as primary or secondary amides, free OH or NH on the aryl halides, which were problematic with the Pd-catalyzed amination methodology. 

Hong (entries 4 and 5), ° and Williams (entries 2 and 8). Whereas many catalysts effectively liberate H2, some require a hydrogen acceptor, such as a ketone or olefin (entries 2, 8, and 9), for effective amide formation. Most of the catalysts mentioned above efficiently couple primary amines and primary alcohols to deliver secondary amides. Difficulties arise when weakly nucleophilic amines (anilines) or more hindered secondary amines are utilised (see Table 12.1 for more detail). 

Formylation reactions have also been found to work with zinc catalysts (Scheme 17.2)." The synthesis of primaiy amides from formic acid and amines requires milder conditions. ZnCla is inexpensive and environmentally benign. Although this method proved successful for the synthesis of primary amides, when longer chain carbojqrlic acids were tested, minimal conversion into the secondary amide was observed, therefore limiting its use for the production of all amides. 

Hydrolysis of primary amides cataly2ed by acids or bases is very slow. Even more difficult is the hydrolysis of substituted amides. The dehydration of amides which produces nitriles is of great commercial value (8). Amides can also be reduced to primary and secondary amines using copper chromite catalyst (9) or metallic hydrides (10). The generally unreactive nature of amides makes them attractive for many appHcations where harsh conditions exist, such as high temperature, pressure, and physical shear. 

The method is not restricted to secondary aryl alcohols and very good results were also obtained for secondary diols [39], a- and S-hydroxyalkylphosphonates [40], 2-hydroxyalkyl sulfones [41], allylic alcohols [42], S-halo alcohols [43], aromatic chlorohydrins [44], functionalized y-hydroxy amides [45], 1,2-diarylethanols [46], and primary amines [47]. Recently, the synthetic potential of this method was expanded by application of an air-stable and recyclable racemization catalyst that is applicable to alcohol DKR at room temperature [48]. The catalyst type is not limited to organometallic ruthenium compounds. Recent report indicates that the in situ racemization of amines with thiyl radicals can also be combined with enzymatic acylation of amines [49]. It is clear that, in the future, other types of catalytic racemization processes will be used together with enzymatic processes. 

Addihon of primary and secondary amines to 1,3-butadiene and isoprene at 0 to 180°C over solid bases such as MgO, CaO, SrO, LajOj, Th02, and ZrOj has also been studied. CaO exhibits the highest achvity, while ZrOj is inachve. MejNH is the most reactive amine, giving primarily the 1,4-addihon product which undergoes iso-merizahon to the enamine N,N-dimethyl-l-butenylamine. It has been proposed that addihon of amines to 1,3-dienes on basic catalysts proceeds via aminoallyl carban-ion intermediates which result from addihon of amide ions to the dienes [169, 170]. 

Phthalimide and N-alkyl-toluenesulfonamide salts are similarly alkylated, and can furthermore be cleaved to polymer-bound secondary and primary amines respectively (57). Potassium pyrrolidonide gives polymer-bound tertiary amide, of interest as a solid cosolvent catalyst ... 

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